As has been the case in the electronics and computer industries, trends in analytical chemical and biochemical instrumentation have been toward miniaturization. In chemical and biochemical analyses, such miniaturization as achieved in e.g., microfluidic systems, provides numerous advantages, including significantly smaller reagent requirements, faster throughput, ready automatability, and in many cases, improved data.
By way of example, U.S. Pat. Nos. 5,498,392 and 5,587,128 describe the performance of amplification reactions in microfabricated devices including microscale flow systems and/or reaction chambers. Such systems substantially reduce the requirements for expensive reagents utilized in amplification reactions. Further, the small scale of these devices also provides for enhanced thermal transfer between heating sources and the reagents in the device.
Similarly, U.S. Pat. No. 5,637,469 describes the use of devices having extremely small internal dimensions for detecting an analyte in a sample via a binding assay. Again, the small scale of such devices provides advantages in terms of small reagent volumes.
Commonly owned Published International Application No. WO 98/00231 describes the use of microfluidic devices and systems in the performance of high-throughput screening assays. Again, these systems reduce the required volumes of potentially very expensive test compounds, e.g., drug candidates, library compounds, etc.
Despite the numerous advantages realized by the miniaturization of analytical systems, such miniaturization can provide difficulties in the use of such system including user handling, reagent delivery or filtration, and system interfacing of such devices.
It would therefore be desirable to provide microfluidic devices that capture the advantages associated with extremely small volumes and dimensions, without the problems associated with such small-scale devices. The present invention meets these and a variety of other needs.
It is a general object of the present invention to provide microfluidic devices and methods that combine the advantages of microfluidics with improved material handling characteristics and reduced costs for manufacturing. The present invention accomplishes this in a first aspect, by providing microfluidic devices that incorporate a body structure comprising at least a first microscale channel network disposed therein. The body structure has a plurality of ports disposed in it, where each port is in fluid communication with one or more channels in the first channel network. The devices also include a cover layer comprising a plurality of apertures disposed therethrough. The cover layer is mated with the body structure whereby each of the apertures is aligned with a separate one of the plurality of ports.
In preferred aspects, each of the body structure and the cover layer separately comprises at least a first surface. The plurality of ports in the body structure are disposed in the first surface of the body structure, and the plurality of apertures in the cover layer are disposed in the first surface of the cover layer. The first surface of the cover layer is mated to the first surface of the body structure such that the apertures align with and are in fluid communication with the ports. In further preferred aspects, the cover layer is fabricated from a polymeric material, and is preferably an injection molded polymeric part.
In one embodiment, the microfluidic devices include a plurality of rings disposed between the cover layer and the body structure with each such ring surrounding one pair of aligned ports and apertures. Each of the rings is optionally molded, e.g., around one or more of the plurality of apertures disposed in the surface of the cover layer and circumferentially around at least one of the plurality of ports aligned with the one or more apertures. Alternatively, the rings are molded around one or more of the plurality of ports disposed in the first surface of the body structure and circumferentially around at least one of the plurality of apertures aligned with the one or more ports. As a further alternative, each of the rings is a separate component from either the cover layer or the body structure; e.g., the rings optionally include a gasket that is placed around one or more port and/or aperture. As separate components, each of the rings is typically placed circumferentially around at least one of the plurality of apertures and circumferentially around at least one of the plurality of ports aligned with one or more of the plurality of apertures.
In another embodiment, the microfluidic devices of the present invention also optionally include a membrane (e.g., a semi-permeable membrane or the like) disposed between at least one pair of aligned apertures and ports, which together form wells, for sieving aggregations of material (e.g., aggregations of cells, molecules, etc.) and/or delivering various reagents to the devices. The membrane is also optionally disposed on or over the wells. The invention additionally includes embodiments in which at least a portion of the wells of the devices include a conductive coating. The use of conductive coatings, inter alia, minimizes cross-contamination between microfluidic devices. Furthermore, the invention also includes other embodiments in which rings, membranes, and/or conductive coatings are used in various combinations in the devices.
The present invention also includes methods of controlling a material composition delivered into a microfluidic device which include flowing a solution that includes the material (e.g., particles, reagents, or the like) through a semi-permeable membrane portion disposed in one or more wells of the devices. Additionally, the methods optionally include immobilizing the material on the semi-permeable membrane prior to delivering the material into the device.
In a related aspect, the present invention provides a microfluidic system that includes a microfluidic device in accordance with the present invention, where the device is further mounted on a controller/detector apparatus that is configured to receive the microfluidic device. The controller/detector apparatus comprises an optical detection system and a material transport system, where the detection system and transport system are operably interfaced with the microfluidic device when the device is mounted on the controller/detector.